DESCRIPTION: (Applicant's Abstract) This application proposes a twin study to determine the heritability of age-related macular degeneration (AMD) which is currently unknown. Study participants are members of the National Academy of Sciences-National Research Council Twin Registry who are currently 71 to 81 years of age. Approximately 50% of the pairs are monozygotic and 50% are dizygotic. The specific aims of the study are to: 1) Determine the heritability of various forms of age-related macular degeneration, or the portion of AMD prevalence due to additive genetic effects, 2) Determine the relative contribution heritability and common environment to the phenotypic variability in ARM, and 3) Estimate the effects of specific genetic mutations and the residual or remaining heritability for various forms of AMD using a partitioned twin analysis. Members of the Twin Registry will be rescreened to identify twins diagnosed with AMD since the initial screening. To achieve adequate statistical power, we will enroll 500 twin pairs: 385 in which one or both twins have AMD and 115 pairs in which neither twin has AMD. The age structure of this unique cohort of elderly twins represents an ideal, although time-limited opportunity to study the genetic determinants of AMD. We propose to achieve the needed sample size to accomplish the specific aims of the study. The results of this study will fill gaps in our knowledge about the genetics of AMD, and will specifically address questions regarding whether and to what extent this disease is heritable, which remain unanswered. The study will provide insight into the pathogenesis of this disorder, and will yield essential information which is needed for the planning of future genetic studies.